Transformed cells in vitro have significantly lower levels of cyclic-AMP than comparable parental lines. The addition of cyclic-AMP or dibutyryl cyclic-AMP to transformed cells inhibits their growth and reverses some of the morphological abnormalities characteristic of transformed cells. Intracellular cyclic AMP levels fluctuate during the cell cycle with the lowest levels observed during mitosis. These in vitro studies suggest cyclic-AMP is a regulating agent infuencing cell growth and differentiation and that transformation to the malignant state involves a defect in cyclic-AMP system leading to low intracellular cyclic-AMP levels resulting in uncontrolled growth. Cyclic-AMP also inhibits the growth of tumor cells in vivo, however, analyses of tumors indicate that tumors have higher rather than lower levels of cyclic-AMP as expected. Experiments are being conducted to determine: 1) if the cyclic-AMP levels of tumor cells growing in vitro are different from those growing in vivo due to differences in environmental factors such as pH, cell density, serum factors etc., 2) if the high level of cyclic-AMP measured in tumor tissue is intracellular or extracellular, and 3) if the extracellular cyclic-AMP in the area of the tumor is advantageous to the growth of the tumor.